What is the expected phenotypic ratio resulting from a homozygous dominant heterozygous cross?

5.9.6. LETHAL GENES AND GENE INTERACTION

There are occasions when a monohybrid cross will produce a homozygous recessive genotype which does not survive. Pure yellow (Ay Ay) mice die before birth. The presence of this lethal condition reduces the 3:1 ratio of F2 to 2:1. Refer to Fig. 68 for a demonstration of this condition.

Genes do not always segregate out as if separate entities having no effects on other genes. Genes do interact in most complex ways. A good demonstration of this situation can be seen in the example shown in Fig. 69.

The Law of Gene Segregation

Mendel carried out a large series of experiments, called monohybrid crosses, over several years of the sort described in Figure 5.4. He did this with each pair of phenotypes shown in Figure 5.3, but we shall use seed (pea) color as an example. Crossing, in the parental generation (P1), true-breeding plants yielding yellow peas with true-breeding plants yielding green ones, Mendel observed hybrid progeny in which all the peas were yellow (the F1 generation). Plants of this F1 generation were allowed to self-fertilize, and the peas of the next generation (F2) were counted and scored. Of more than 8,000 peas collected, 6,022 were yellow and 2,001 were green—an almost perfect ratio of 3 yellow to 1 green. Using each of the other six characters, Mendel obtained the same result—self-fertilization of the single character observed in the F1 yielded both parental characters in the F2 at a ratio of 3 : 1.

These findings were incompatible with the idea of blending. Each parental character was recovered intact in the F2, rather than being “lost” in the F1. Mendel reasoned that the yellow peas in the P1 were not identical to the yellow peas in the F1 because the P1 yellows were true breeding and the F1 yellows were not. He proposed that the trait which appeared in the F1 was dominant and that the trait which disappeared in the F1 but reappeared in the F2 was recessive. But what accounted for the reproducible 3 : 1 ratio?

Mendel proposed—in an astonishingly prescient way—that each plant carried two copies of a unit of inheritance for each trait, one inherited from the male, one from the female. He proposed further that each unit comes in alternative forms that give rise to the differentiating characteristics he studied (yellow–green, round–wrinkled, etc.). Today, we call his “units” “genes” and his “alternative forms” “alleles.” He went on to propose that the two alleles found in cells of a mature plant segregate (separate) during germ cell formation and reunite, one from each parent, at fertilization. Mendel set out to find laws of inheritance. This was his first: the law of gene segregation.

The law explains the 3 : 1 ratio in the F2 as follows (Figure 5.4), using the visually accessible Punnett square (a diagram that is used to predict an outcome of a particular cross or breeding experiment). The true-breeding yellow pea plants (P1) have two copies of the dominant allele, denoted Y; the plants yielding only green peas have two copies of the recessive allele, denoted y. (Capital letters generally depict the dominant allele, small letters the recessive one.) Gametes of these P1 plants (YY and yy, referred to as “homozygotes”) are either Y or y. At fertilization, all zygotes are Yy (heterozygotes). Because Y is dominant, all plants are yellow. When these plants are self-fertilized, the male and female each produce gametes that are either Y or y. In the F2, then, 1/4 of the progeny are YY, 1/4 are Yy, 1/4 are yY, and 1/4 are yy. Given that Y is dominant, and that Yy and yY are equivalent, the ratio between yellow and green peas is 3 : 1.

Monohybrid Cross and Test Cross

Mendel's cross-hybridization studies involved purebred plants that differed with regard to a single contrasting trait. Purebred, homozygous, parental stocks were crossed and the offspring of this cross are called F1 hybrids, or monohybrids. In the F1 generation, all of the hybrids resembled the parent with the dominant trait. The genotype of these monohybrid, or heterozygous, plants can be represented as genotype Aa, with the uppercase letter representing the dominant allele and the lowercase letter representing the recessive allele. The F1 hybrid plants were next self-fertilized (Aa×Aa) and this cross is known as a monohybrid cross. In the offspring of monohybrid crosses, or F2 generation, Mendel repeatedly observed a phenotype ratio of three plants with the dominant phenotype to one plant with the recessive phenotype (3:1 phenotype ratio) in the F2 generation. Mendel predicted that the plants with a dominant phenotype in the F2 generation were of mixed genotypes with some being homozygous dominant genotype AA and others being heterozygous genotype Aa. In order to determine the genotypes of plants with dominant phenotypes in the F2 generation Mendel devised the test cross.

The test cross takes the organism with a dominant phenotype but unknown genotype and crosses it to a homozygous recessive individual with a known genotype aa. In a test cross with a plant of genotype AA all offspring will have the dominant phenotype and will have the heterozygous genotype Aa. However, if a plant with genotype Aa is used in a test cross, then the genotypes of 50% of the offspring will have the genotype Aa and display the dominant trait. The other 50% will be display the recessive phenotype since they will have the homozygous recessive genotype aa. Mendel's test cross method is still used today in breeding procedures with plants and animals in order to determine the genotype of plants with dominant phenotypes.

The First Generation from the Hybrids, and Beyond

The fifth section of Mendel’s paper shows, repeatedly, that the dominant and recessive forms of each trait appear in a 3:1 ratio in the progeny of hybrids crossed to each other. The numbers speak for themselves in Table 3. Mendel showed the classic 3:1 phenotypic ratio of a monohybrid cross (one trait present in two forms, or alleles), although the terms ‘phenotype’ (an individual’s appearance) and ‘genotype’ (the gene variants present) were not yet in use. This observation would become known as Mendel’s first law, or the law of segregation, years later (Figure 1). The ratios that Mendel chronicled were actually the result of meiosis, the type of cell division that gives rise to gametes. When a sperm or egg forms, the chromosome pairs (homologous pairs), whose DNA has been replicated, separate. Likewise, the pairs of genes that comprise the chromosomes separate and are distributed into different gametes. The part of meiosis that determines the gene combinations that will enter gametes, and eventually be expressed in organisms, is called metaphase, when chromosomes align down the center of the cell.

Table 3. The ‘first generation from the hybrids’ experiments reveal a 3:1 dominant-to-recessive phenotypic ratio

Mendel followed crosses beyond the third generation, determining that the dominant-appearing individuals among the progeny of the hybrids had ‘double signification’, meaning that they were of two types. He wrote, “… of those forms which possess the dominant character in the first generation, two-thirds have the hybrid character, while one-third remains constant with the dominant character.” One type bred true, always yielding the dominant phenotype in further crosses. The second type, when crossed to hybrids, produced both the dominant and recessive phenotypes. The plants that did not breed true outnumbered the other plants two to one.

Today, we call the dominant-appearing plants that are ‘constant’ homozygous dominant. They have two copies of the dominant allele. The hybrids, called heterozygotes, have one dominant and one recessive allele. Individuals expressing the recessive trait constitute the homozygous recessive class, and they too breed true. That is, when crossed among themselves, they yield only homozygous recessive individuals. A monohybrid cross results in a phenotypic ratio of 3:1 (dominant to recessive), and a genotypic ratio of 1:2:1 (homozygous dominant to heterozygous to homozygous recessive).

Mendel carried out crosses for four to six generations for each of the seven traits, each time self-crossing the individuals that ‘bred true’ (the homozygous dominants and homozygous recessives) as well as self-crossing the hybrids. When he did this repeatedly, the proportion of hybrids decreased by 50% at each generation. By the 10th generation, only two hybrids would remain for every 1023 individuals of each homozygous class.